841 research outputs found

    Rumination-focused cognitive behaviour therapy vs. cognitive behaviour therapy for depression:Study protocol for a randomised controlled superiority trial

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    BACKGROUND: Cognitive behavioural therapy is an effective treatment for depression. However, one third of the patients do not respond satisfactorily, and relapse rates of around 30 % within the first post-treatment year were reported in a recent meta-analysis. In total, 30–50 % of remitted patients present with residual symptoms by the end of treatment. A common residual symptom is rumination, a process of recurrent negative thinking and dwelling on negative affect. Rumination has been demonstrated as a major factor in vulnerability to depression, predicting the onset, severity, and duration of future depression. Rumination-focused cognitive behavioural therapy is a psychotherapeutic treatment targeting rumination. Because rumination plays a major role in the initiation and maintenance of depression, targeting rumination with rumination-focused cognitive behavioural therapy may be more effective in treating depression and reducing relapse than standard cognitive behavioural therapy. METHOD/DESIGN: This study is a two-arm pragmatic randomised controlled superiority trial comparing the effectiveness of group-based rumination-focused cognitive behaviour therapy with the effectiveness of group-based cognitive behavioural therapy for treatment of depression. One hundred twenty-eight patients with depression will be recruited from and given treatment in an outpatient service at a psychiatric hospital in Denmark. Our primary outcome will be severity of depressive symptoms (Hamilton Rating Scale for Depression) at completion of treatment. Secondary outcomes will be level of rumination, worry, anxiety, quality of life, behavioural activation, experimental measures of cognitive flexibility, and emotional attentional bias. A 6-month follow-up is planned and will include the primary outcome measure and assessment of relapse. DISCUSSION: The clinical outcome of this trial may guide clinicians to decide on the merits of including rumination-focused cognitive behavioural therapy in the treatment of depression in outpatient services. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02278224, registered 28 Oct. 2014

    Space based astronomy: Teacher's guide with activities

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    This curriculum guide uses hands-on activities to help students and teachers understand the significance of space-based astronomy - astronomical observations made from outer space. The guide contains few of the traditional activities found in many astronomy guides such as constellation studies, lunar phases, and planetary orbits. Instead, it tells the story of why it is important to observe celestial objects from outer space and how to study the entire electromagnetic spectrum. The guide begins with a survey of astronomy related NASA spacecraft. This is followed by a collection of activities in four units: (1) the atmospheric filter; (2) the electromagnetic spectrum; (3) collecting electromagnetic radiation; and (4) down to Earth. A curriculum index identifies the curriculum areas each activity addresses. The guide concludes with a glossary, reference list, a NASA Resources list, and an evaluation card. It is designed for students in grades 5 through 8

    The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

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    The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

    Phase II trial of Modified Vaccinia Ankara (MVA) virus expressing 5T4 and high dose Interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma

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    <p>Abstract</p> <p>Background</p> <p>Interleukin-2 (IL-2) induces durable objective responses in a small cohort of patients with metastatic renal cell carcinoma (RCC) but the antigen(s) responsible for tumor rejection are not known. 5T4 is a non-secreted membrane glycoprotein expressed on clear cell and papillary RCCs. A modified vaccinia virus Ankara (MVA) encoding 5T4 was tested in combination with high-dose IL-2 to determine the safety, objective response rate and effect on humoral and cell-mediated immunity.</p> <p>Methods</p> <p>25 patients with metastatic RCC who qualified for IL-2 were eligible and received three immunizations every three weeks followed by IL-2 (600,000 IU/kg) after the second and third vaccinations. Blood was collected for analysis of humoral, effector and regulatory T cell responses.</p> <p>Results</p> <p>There were no serious vaccine-related adverse events. While no objective responses were observed, three patients (12%) were rendered disease-free after nephrectomy or resection of residual metastatic disease. Twelve patients (48%) had stable disease which was associated with improved median overall survival compared to patients with progressive disease (not reached vs. 28 months, p = 0.0261). All patients developed 5T4-specific antibody responses and 13 patients had an increase in 5T4-specific T cell responses. Although the baseline frequency of Tregs was elevated in all patients, those with stable disease showed a trend toward increased effector CD8+ T cells and a decrease in Tregs.</p> <p>Conclusion</p> <p><b>V</b>accination with MVA-5T4 did not improve objective response rates of IL-2 therapy but did result in stable disease associated with an increase in the ratio of 5T4-specific effector to regulatory T cells in selected patients.</p> <p>Trial registration number</p> <p>ISRCTN83977250</p

    Comparison of measures of marker informativeness for ancestry and admixture mapping

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    <p>Abstract</p> <p>Background</p> <p>Admixture mapping is a powerful gene mapping approach for an admixed population formed from ancestral populations with different allele frequencies. The power of this method relies on the ability of ancestry informative markers (AIMs) to infer ancestry along the chromosomes of admixed individuals. In this study, more than one million SNPs from HapMap databases and simulated data have been interrogated in admixed populations using various measures of ancestry informativeness: Fisher Information Content (FIC), Shannon Information Content (SIC), F statistics (F<sub>ST</sub>), Informativeness for Assignment Measure (I<sub>n</sub>), and the Absolute Allele Frequency Differences (delta, δ). The objectives are to compare these measures of informativeness to select SNP markers for ancestry inference, and to determine the accuracy of AIM panels selected by each measure in estimating the contributions of the ancestors to the admixed population.</p> <p>Results</p> <p>F<sub>ST </sub>and I<sub>n </sub>had the highest Spearman correlation and the best agreement as measured by Kappa statistics based on deciles. Although the different measures of marker informativeness performed comparably well, analyses based on the top 1 to 10% ranked informative markers of simulated data showed that I<sub>n </sub>was better in estimating ancestry for an admixed population.</p> <p>Conclusions</p> <p>Although millions of SNPs have been identified, only a small subset needs to be genotyped in order to accurately predict ancestry with a minimal error rate in a cost-effective manner. In this article, we compared various methods for selecting ancestry informative SNPs using simulations as well as SNP genotype data from samples of admixed populations and showed that the I<sub>n </sub>measure estimates ancestry proportion (in an admixed population) with lower bias and mean square error.</p

    Genotype, haplotype and copy-number variation in worldwide human populations

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    Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups(1-3). Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms ( SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected-including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas-the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62552/1/nature06742.pd
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